This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Peripheral arterial disease (PAD) is a form of lower extremity atherosclerosis estimated to affect 8-12 million Americans. A progression of limb atherosclerosis may result in critical tissue ischemia, causing disabling intermittent claudication, rest pain and limb loss. The most commonly used diagnostic parameter of PAD is Ankle/Brachial index (ABI), which measures the ratio of ankle and brachial systolic pressures. It is generally agreed that an ABI<0.95 is abnormal. However, ABI does not correlate well with impairment in exercise test (e.g. walking distance). Other non-invasive diagnostic techniques include Duplex Ultrasound, Magnetic Resonance Angiographic (MRA), and Exercise Testing. We have pursued a novel approach to simultaneously assess micro-vascular blood flow and oxygenation consumption in the ischemic muscles using Diffuse Optical Spectroscopy (DOS) and Diffuse Correlation Spectroscopy (DCS): these continuous, non-invasive, and inexpensive monitoring techniques may allow for further understanding of the pathophysiology of PAD. DOS can continuously measure oxy-hemoglobin and deoxy-hemoglobin concentrations in deep tissues (depth up to several centimeters). DCS is sensitive to blood flow in smaller vessels such as arterioles, capillaries, and venules, unlike Duplex Ultrasound, which is primarily sensitive to large vessels. DOS and DCS data is of high temporal (~100 ms), but relatively low spatial resolution (>5 mm). In this project, diffuse optical spectroscopy (DOS) measurement will be performed on patients with PAD and healthy subjects. Three challenges will be introduced for each subject: cuff ischemia (femoral artery), treadmill , and plantar flexion. We expect to observe changes in blood oxygenation, volume, and blood flow change during test.